Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers:A case report and review of literature

BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant literature.CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark stools.At the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic abscess.The surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess removal.The patient’s condition improved and he was dis-charged.However,the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge.On the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve significantly.Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes.ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation,respectively.This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes.Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms.CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD.Orally administered Kangfuxin liquid may have therapeutic potential.

Increased succinate receptor GPR91 involved in the pathogenesis of Mooren's ulcer

AIM： To investigate the expression of succinate receptor GPR91 and its pathogenic roles in Mooren＇s ulcer（MU）.METHODS： Biopsy specimens were obtained from 7 patients with MU and 6 healthy donors. The expression of GPR91 in MU tissues was evaluated using quantitative realtime reverse transcription polymerase chain reaction（qRTPCR） and immunohistochemistry（IHC）. Succinate was used to activate GPR91 signaling, and the effect of GPR91 on the expression of interleukin-1β（IL-1β）, NLRP3, vascular endothelial growth factor（VEGF） and matrix metalloproteinase-13（MMP-13） in human peripheral blood mononuclear cells（PBMCs） was determined. The influence of GPR91 on the nuclear factor-κB（NF-κB） signaling in PBMCs was investigated by detecting the phosphorylation of p65. Moreover, the expression of IL-1β, VEGF, MMP-13 and phosphorylated p65（p-p65） in the tissues of MU was examined by qRT-PCR or IHC.RESULTS： GPR91 mRNA expression showed a higher level in the MU group than in the healthy control group. IHC analysis also revealed that the expression of GPR91 was elevated in patients with MU compared with healthy controls. Moreover, ligation of GPR91 with succinate promoted the lipopolysaccharide-induced production of NLRP3, IL-1β, VEGF and MMP-13 in PBMCs through increased phosphorylation of p65. Pharmacological inhibition of the NF-κB signaling reversed GPR91 induced production of NLRP3, IL-1β, VEGF and MMP-13. These findings, coupled with the elevated amounts of IL-1β, VEGF, MMP-13 and p-p65 observed in the MU biopsies, constituted a rational basis for the involvement of GPR91 in the pathogenesis of MU.CONCLUSION： This study indicates the increased succinate receptor GPR91 in conjunctival or corneal tissues is involved in the pathogenesis of MU through elevated NF-κB activity, which may provide a new therapeutic target for MU.

Diagnostic delay in inflammatory bowel diseases in a German population

BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists.AIM To identify risk factors leading to prolonged diagnostic time in a German IBD cohort.METHODS Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis.Total diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time period.RESULTS The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;P<0.001),mainly due to increased physician diagnostic time(5.5 vs 1.0 mo;P<0.001).In a multivariate analysis,the predominant symptoms diarrhea(P=0.012)and skin lesions(P=0.028)as well as performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD patients.In UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic time.CONCLUSION We demonstrated that CD patients compared to UC are at risk of long diagnostic delay.Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients.

Increased cGAS/STING signaling components in patients with Mooren's ulcer

AIM:To explore the expression of cGAS/STING signaling components in Mooren’s ulcer(MU).METHODS:Samples were obtained from ten MU patients,and eight residual corneal-scleral rings of healthy donor corneas for controls.Human corneal epithelial cells(HCECs)were used to evaluate the effect of cGAS/STING signaling pathway.Immunohistochemistr y(IHC)and Western blot were used to examine the expression of cGAS,STING,and phosphorylated interferon regulatory factor 3(p-IRF3)in MU tissues.The expression of interferon-β(IFN-β)and interferon-stimulated genes(ISGs)was quantified by real-time polymerase chain reaction(PCR)and enzymelinked immunosorbent assay(ELISA).RESULTS:The protein levels of cGAS and STING in MU samples were significantly elevated when compared with the healthy controls by Western blot and IHC.After stimulation with cGAMP,real-time PCR and ELISA showed a dramatic increase of IFN-βand ISGs(containing CXCL10,IFIT1,and IL-6)in HCECs.Moreover,HCECs treated with cGAMP was characterized by increased phosphorylation and more nuclear translocation of IRF3.Meanwhile,increased p-IRF3 was observed in MU samples via IHC and Western blot.CONCLUSION:The pronounced expression of cGAS/STING signaling components in the patients with MU and probably contribute to the onset and development of MU.

Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients’questions?An evidencecontrolled analysis

Artificial intelligence is increasingly entering everyday healthcare.Large language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM tools.The hype generated by such systems may lead to unweighted patient trust in these systems.Therefore,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for patients.This review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists.From the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases.Further studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.

More on the interplay between gut microbiota,autophagy,and inflammatory bowel disease is needed

The concept of inflammatory bowel disease(IBD),which encompasses Crohn’s disease and ulcerative colitis,represents a complex and growing global health concern resulting from a multifactorial etiology.Both dysfunctional autophagy and dysbiosis contribute to IBD,with their combined effects exacerbating the related inflammatory condition.As a result,the existing interconnection between gut microbiota,autophagy,and the host’s immune system is a decisive factor in the occurrence of IBD.The factors that influence the gut microbiota and their impact are another important point in this regard.Based on this initial perspective,this manuscript briefly highlighted the intricate interplay between the gut microbiota,autophagy,and IBD pathogenesis.In addition,it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context.Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms,which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.

Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic disrupted healthcare in the United States.AIM To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease(IBD)decedents.METHODS We performed a register-based study using data from the National Vital Statistics System,which reports death data from over 99%of the United States population,from January 1,2006 through December 31,2021.IBD-related deaths among adults 25 years and older were stratified by age,sex,race/ethnicity,place of death,and primary cause of death.Predicted and actual age-standardized mortality rates(ASMRs)per 100000 persons were compared.RESULTS 49782 IBD-related deaths occurred during the study period.Non-COVID-19-related deaths increased by 13.14%in 2020 and 18.12%in 2021[2020 ASMR:1.55 actual vs 1.37 predicted,95%confidence interval(CI):1.26-1.49;2021 ASMR:1.63 actual vs 1.38 predicted,95%CI:1.26-1.49].In 2020,non-COVID-19-related mortality increased by 17.65%in ulcerative colitis(UC)patients between the ages of 25 and 65 and 36.36%in non-Hispanic black(NHB)Crohn’s disease(CD)patients.During the pandemic,deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased.CONCLUSION IBD patients suffered excess non-COVID-19-related death during the pandemic.Excess death was associated with younger age among UC patients,and with NHB race among CD patients.Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

Changes in Local Immune Functions in Mooren's Ulcer

Purpose: To the investigate changes in local immune functions of the cornea and the adjacent conjunctiva, and their roles in the mechanism of the disease. Method: The cornea and adjacent bulbar conjunctiva taken from 14 patients with Mooren’s ulcer were stained immunohistochemically for CD3, CD4, CD8, HLA-DR, GD1 and CD25.Result: An aberrant expression of HLA-DR antigen by a large number of kerato-conjunctival epithelial cells and keratocytes in the corneal stroma was found. The CD4 + /CD8+ ratio is significantly higher than normal control. Conclusion: The aberrant expression of MHC- II antigen in the resident cells at the peripheral cornea and the adjacent conjunctiva, along with a raised local TH/ Ts ratio leading to an excessive autoimmune reactivity is possibly the direct cause of Mooren’s ulcer. Eye Science 1996; 12: 33-35.

Fresh Amniotic Membrane Transplantation Combined Lamellar Keratoplasty for Patients with Recurrent Mooren's Ulcer

Purpose: To investigate the possibility of amniotic membrane as an immunologicalinsulating band to reduce the recurrent frequency of Mooren's ulcer.Methods: Twelve cases(12 eyes)with recurrent Mooren's Ulcer were observed. Amongthem, 4 cases(4 eyes)were male and 8 cases(8 eyes) female, ranging in age between 26and 51 years[mean(41 ± 3)years]. Three eyes recurred once, 5 eyes twice, and 4 eyesthree before. Eleven of 12 cases (11/12 eyes)with frequently recurrent Mooren's ulcerunderwent lamellar keratoplasty combined amniotic membrane transplantation(AMT).One patient who had entire corneal ulceration accepted AMT alone.Results: Follow-up time is 12 to 29 months, [mean (23 ± 6) months]. Before AMT, therecurrent frequency of Mooren's Ulcer of all cases after corneal surgery was 1 ～ 7 months[mean(3 ± 2)months]. Nine of 12 eyes with lamellar keratoplasty combined AMT did notrecur within the observation period; 2 eyes recurred 11 months after the surgery. Threemonths postoperatively, neovascularization was observed, which made it nearly impossibleto decipher between amniotic membrane and its nearby conjunctiva, only at the junctionof the transplant can some trails be observed. One case with entire AMT alone showedgraft resolution and neovascularization in 1 month.Conclusion:AMT combined with lamellar keratoplasty and lesion excision may delayrecurrence of Mooren's Ulcer, reduce its recurrent frequency. Besides the effects ofdecreasing inflammation, it may have immunological insulating function as well. Thisconclusion should be proven by further clinical comparative study of much moresamples.

A Study of Clinical Characteristics and Treatment of Mooren's Ulcer

Objective: To investigate the clinical characteristics and to compare the effects of several therapies of Mooren's corneal ulcer.Methods: 550 consecutive cases of Mooren's corneal ulcer inpatients were analysed, including the age, sex, laterality of the eye, ulcer location , perforative rate, cure rate of surgeries, recurrent rate, and the effects of conjunctiva excision, lamellar keratoplasty (LKP), LKP and plus cyclosporin A eye drop.Results: The average age of onset of the cornea! ulcer was 48.4 years old, the ratio of the male to the female patients was 1:0.74, the bilateral disease was 30% of the total cases, 31.5% of the bilateral disease occurred in the younger group, and 68.5% of the bilateral ulcer occurred in the older group, ulcers located at the limbus of the palpebral fissure were 70% of the total cases, perforative rate was 13.3% , 43.2% of the perforation occurred in the younger group, and 56.8% of the perforation occurred in the older group, recurrent rate of the post-opertion was 25.6%,

MicroRNAs in inflammatory bowel disease:What do we know and what can we expect?

MicroRNAs(miRNAs),small non-coding RNAs composed of 18–24 nucleotides,are potent regulators of gene expression,contributing to the regulation of more than 30%of protein-coding genes.Considering that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells,there is an interest in exploring their importance in inflammatory bowel disease(IBD).IBD is a chronic and multifactorial disease of the gastrointestinal tract;the main forms are Crohn's disease and ulcerative colitis.Several studies have investigated the dysregulated expression of miRNAs in IBD,demonstrating their important roles as regulators and potential biomarkers of this disease.This editorial presents what is known and what is expected regarding miRNAs in IBD.Although the important regulatory roles of miRNAs in IBD are clearly established,biomarkers for IBD that can be applied in clinical practice are lacking,emphasizing the importance of further studies.Discoveries regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea,2010-2018

BACKGROUND Inflammatory bowel disease(IBD)was previously regarded as a Western disease;however,its incidence is increasing in the East.The epidemiology of IBD in Asia differs significantly from the patterns in the West.AIM To comprehensively investigate the epidemiology of IBD in South Korea,inclu-ding its incidence,prevalence,medication trends,and outcomes.METHODS We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases(RIDs),operated by the National Health Insurance Service of South Korea.Patients with IBD were identified based on the International Classification of Diseases,Tenth Revision,and RID diagnostic codes for Crohn’s disease(CD)and ulcerative colitis(UC)from 2010 to 2018.RESULTS In total,14498 and 31409 patients were newly diagnosed with CD and UC,respectively,between 2010 and 2018.The annual average incidence of CD was 3.11 cases per 105 person-years,and that of UC was 6.74 cases per 10^(5) person-years.Since 2014,the incidence rate of CD has been stable,while that of UC has steadily increased,shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018.The CD and UC prevalence increased consistently over the study period;the use of 5-aminosali-cylates and corticosteroids gradually decreased,while that of immunomodulators and biologics steadily increased in both CD and UC.The clinical outcomes of IBD,such as hospitalization and surgery,decreased during the study period.CONCLUSION The CD incidence has been stable since 2014,but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018.IBD clinical outcomes improved over time,with increased use of immunomodu-lators and biologics.

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.

Diagnostic delay in inflammatory bowel disease:Current situation and problems

In this article,we comment on the article by Blüthner et al published recently.Inflammatory bowel disease(IBD),including ulcerative colitis and Crohn’s disease,is a chronic relapsing and remitting condition primarily as a consequence of intestinal inflammation.It is important about adopting early and effective treatment to control clinical symptoms of IBD patients.Diagnostic delay can lead to adverse clinical outcomes and increase disease burden.Diagnostic delay is multifactorial.There are some factors related to diagnostic delay,such as patient factors and healthcare factors.We focus on the diagnostic tools for IBD,the outcomes and factors of diagnostic delay of IBD.

Inflammatory bowel disease and risk of ophthalmic inflammation-related diseases:a two-sample Mendelian randomization study

AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcerative colitis(UC),and Crohn’s disease(CD)were derived from the largest genome-wide association studies(GWAS)published to date.The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis,keratitis,iridocyclitis,chorioretinitis,episcleritis,and optic neuritis.All participants were of European ancestry.Three methods which included inverse variance weighting(IVW),weighted median(WM),and MR-Egger regression were performed to estimate the causal association in this study.IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes,to summarize the effect sizes of multiple independent studies,which could provide the most precise estimated results.IVW was used as the primary outcome,while WM and MR-Egger were used to improve the estimation of IVW.RESULTS:A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis,keratitis,iridocyclitis,and optic neuritis,but not on chorioretinitis or episcleritis.After Bonferroni correction,the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis(IVW:OR,1.17;95%CI,1.10-1.24,P=2.54×10^(-7)).CD was significantly associated with conjunctivitis(IVW:OR,1.05;95%CI,1.03-1.08,P=3.20×10^(-5)),keratitis(IVW:OR,1.06;95%CI,1.02-1.09;P=1.13×10^(-3)),and iridocyclitis(IVW:OR,1.09;95%CI,1.04-1.14;P=1.43×10^(-4)).CONCLUSION:IBD causally poses a risk of inflammation of conjunctiva,cornea,Iris-ciliary body complex,and optic neuritis.CD is more closely associated with the eye inflammation than UC.These impliy that the relationship of IBD and different parts of the eye structure are different,and provide novel evidence linking based on the association of the gut-eye axis.

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many others.AIM To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases.An additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with IBD.METHODS This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched controls.All patients underwent an extensive workup,including colonoscopy with subsequent histopathological analysis.Disease activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring systems.GDF-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence immunoassay.RESULTS In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was established.Specifically,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to IBD patients with normal hemoglobin levels,GDF-15 serum levels were higher in patients with anemia(1256(502-2100)pg/mL vs 444(412-795)pg/mL,P<0.001).CONCLUSION For the first time,we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls,and the results imply that GDF-15 might be involved in IBD pathophysiology.Yet,it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Discontinuation of therapy in inflammatory bowel disease: Current views

The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences.

Evaluating the role of large language models in inflammatory bowel disease patient information

This letter evaluates the article by Gravina et al on ChatGPT’s potential in providing medical information for inflammatory bowel disease patients.While promising,it highlights the need for advanced techniques like reasoning+action and retrieval-augmented generation to improve accuracy and reliability.Emphasizing that simple question and answer testing is insufficient,it calls for more nuanced evaluation methods to truly gauge large language models’capabilities in clinical applications.

Does type 1 diabetes serve as a protective factor against inflammatory bowel disease:A Mendelian randomization study

BACKGROUND The impact of type 1 diabetes(T1D)on inflammatory bowel disease(IBD)remains unclear.AIM To analyze the causal relationship between T1D and IBD using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms were sourced from FinnGen for T1D,IBD,ulcerative colitis(UC)and Crohn’s disease(CD).Inverse variance-weighted,MREgger,and weighted median tests were used to assess exposure-outcome causality.The MR-Egger intercept was used to assess horizontal pleiotropy.Cochran’s Q and leave-one-out method were used to analyze heterogeneity and sensitivity,respectively.RESULTS Our MR analysis indicated that T1D was associated with a reduced risk of IBD[odds ratio(OR):0.959;95%confidence interval(CI):0.938-0.980;P<0.001]and UC(OR:0.960;95%CI:0.929-0.992;P=0.015),with no significant association observed in terms of CD risk(OR:0.966;95%CI:0.913-1.022;P=0.227).The MR-Egger intercept showed no horizontal pleiotropy(P>0.05).Cochran’s Q and leave-one-out sensitivity analyses showed that the results were not heterogeneous(P>0.05)and were robust.CONCLUSION This MR analysis suggests that T1D serves as a potential protective factor against IBD and UC but is independent of CD.